ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Cerebral infusion of AAV9 vector-encoding non-self proteins can elicit cell-mediated immune responses.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 107 citations in OpenAlex.
- Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus.Fluids and barriers of the CNS · 2026Article
- Retrograde transduction of dopaminergic cells in substantia nigra of the rhesus monkey.Scientific reports · 2026Article
- Retrograde transduction of dopaminergic cells in substantia nigra of rhesus monkey.bioRxiv : the preprint server for biology · 2026Article
- MicroRNA-mediated neuronal detargeting alters astrocyte cell fate conversion trajectories in vivo.Communications biology · 2025Article
- Early postnatal expression mitigates immune responses to Cas9 in the murine central nervous system.Molecular therapy. Methods & clinical development · 2025Article
- Delivery of AAV vectors to the superior olivary complex enables efficient adult cochlear transduction via axonal transport.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies.Gene therapy · 2025Review
- An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.Gene therapy · 2024Article
- AAV8 vector induced gliosis following neuronal transgene expression.Frontiers in neuroscience · 2024Article
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Efficacy of Adeno-Associated Virus Serotype 9-Mediated Gene Therapy for AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain.Nature communications · 2023Article
- Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Immunogenicity of CRISPR therapeutics-Critical considerations for clinical translation.Frontiers in bioengineering and biotechnology · 2023Review
- The engineered AAV2-HBKO promotes non-invasive gene delivery to large brain regions beyond ultrasound targeted sites.Molecular therapy. Methods & clinical development · 2022Article
- Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery.Molecular therapy. Methods & clinical development · 2022Article
- Reduced Immunogenicity of Intraparenchymal Delivery of Adeno-Associated Virus Serotype 2 Vectors: Brief Overview.Current gene therapy · 2022Review
- Transgene distribution and immune response after ultrasound delivery of rAAV9 and PHP.B to the brain in a mouse model of amyloidosis.Molecular therapy. Methods & clinical development · 2021Article
- Retrograde Transgene Expression via Neuron-Specific Lentiviral Vector Depends on Both Species and Input Projections.Viruses · 2021Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
There is considerable interest in the use of adeno-associated virus serotype 9 (AAV9) for neurological gene therapy partly because of its ability to cross the blood-brain barrier to transduce astrocytes and neurons. This raises the possibility that AAV9 might also transduce antigen-presenting cells (APC) in the brain and provoke an adaptive immune response. We tested this hypothesis by infusing AAV9 vectors encoding foreign antigens, namely human aromatic L-amino acid decarboxylase (hAADC) and green fluorescent protein (GFP), into rat brain parenchyma. Over ensuing weeks, both vectors elicited a prominent inflammation in transduced brain regions associated with upregulation of MHC II in glia and associated lymphocytic infiltration. Transduction of either thalamus or striatum with AAV9-hAADC evinced a significant loss of neurons and induction of anti-hAADC antibodies. We conclude that AAV9 transduces APC in the brain and, depending on the immunogenicity of the transgene, can provoke a full immune response that mediates significant brain pathology. We emphasize, however, that these observations do not preclude the use of AAV serotypes that can transduce APC. However, it does potentially complicate preclinical toxicology studies in which non-self proteins are expressed at a level sufficient to trigger cell-mediated and humoral immune responses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.